Ivy Foundation funding supports study of p75 neurotrophin receptor as a drug target in malignant Glioma

Dr. Peter Forsyth and colleagues have been awarded a total of $1,277,005 over 3 years by the Ben & Catherine Ivy Foundation to develop and test novel inhibitors of the p75 neurotrophin receptor that could help prevent malignant glioma cells from spreading into surrounding normal brain.

Although invasion of malignant glioma cells into normal brain tissue is a major cause of disease progression and treatment failure, the biological mechanisms that drive this process are poorly understood. Work in the Forsyth lab has revealed that one key molecule controlling this process appears to be the p75 neurotrophin receptor. This protein is expressed robustly in 80% of GBM patient specimens and is activated following processing by the membrane-bound gamma-secretase enzyme.

With the support of the Ivy Foundation’s funding, the Forsyth lab will develop and test novel and known inhibitors of gamma-secretase as potential drug candidates for the treatment of gliomas in preclinical laboratory models of the disease. These studies will determine whether or not these agents are capable of inhibiting p75-mediated brain tumour invasion. If this therapeutic strategy proves sufficiently promising in these initial studies, it may lead to a clinical trial in patients with recurrent malignant glioma, either as a single therapy, or in combination with an anti-angiogenic agent.